Effect of ABCB1 Polymorphisms on Darunavir Plasma and Intracellular Concentrations
(2017) 16th European AIDS conference — Location: (Italy) Minalo (25.October.2017)
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- OBJECTIVES: Genetic variability in ABCB1 has been associated with differences in drug plasma and intracellular concentrations of protease inhibitors (PI). The aim of the present study was to investigate the effect of ABCB1 polymorphisms (1199G>A, 1236C>T, 2677G>T/A, 3435C>T) on darunavir (DRV) exposure in plasma and in peripheral blood mononuclear cells (PBMCs) but also on virological response in a cohort of HIV-1 infected patients. METHODS: 135 HIV-1 infected patients treated with DRV-based therapy were included in the study. Blood samples were obtained just before drug intake in order to determine through plasma ([DRV]plasma) and cell associated ([DRV]CC)concentrations using an ultra-performance liquid chromatography method (UPLC) with diode-array detection (DAD) and a high-performance liquid chromatography tandem mass spectrometry method (LC-MS-MS), respectively. ABCB1 genotyping were determined using TaqMan® real-time PCR technology. RESULTS: 135 HIV-1 infected patients were included. 69% received DRV/r 800/100mg once-a- day while 31% received 600/100mg twice-a-day. 76% had an undetectable viral load (< 37 copies/ml). The ABCB1 1199A, 1236T, 2677 T/A and 3435T alleles showed a frequency of 3.7%, 28%, 24% and 50%, respectively. [DRV]plasma and [DRV]CC were evaluated in 135 and 127 patients, respectively. The geometric mean of [DRV]plasma and [DRV]CC were 1805 ng/ml (CI95%=[1593-2045]) and 324.5 ng/ml (CI95%=[268.2-392.5]), respectively and were not significantly different in ABCB1 variant allele carriers when compared to wild-type homozygous group, whatever the SNP concerned. The virological response to treatment was not affected by any of the studied ABCB1 polymorphisms. CONCLUSION: Neither [DRV]plasma nor [DRV]CC was affected by any of the investigated ABCB1 SNPs suggesting that DRV pharmacokinetic inter-individual variability is not explained by ABCB1 genetic variations.
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Belkhir, L., Vandercam, B., Haufroid, V., & Elens, L. (2017). Effect of ABCB1 Polymorphisms on Darunavir Plasma and Intracellular Concentrations. 16th European AIDS conference, (Italy) Minalo. https://hdl.handle.net/2078.5/172142